Pedigrees were constructed from family histories of patients participating in a dementia program to examine the genetic basis of Alzheimer's disease. Differences in family history between monozygotic twins discordant or concordant for dementia of the Alzheimer type suggest heritable and nonheritable forms of Alzheimer's disease. A longitudinal study of three monozygotic twin pairs discordant for dementia of the Alzheimer type showed continued discordance in brain metabolism, anatomy and cognitive variables for 9-11 years, arguing for nonheritable factors in Alzheimer's disease. Experimental protocols were developed for comparing phenotypes and genotypes of individuals with duplications of parts of chromosome 21, to identify genes contributing to mental retardation and dementia. Buffy coats from blood of first degree relatives with dementia of the Alzheimer type were injected into hamsters to test transmissibility in Alzheimer's disease. In animals surviving up to 250 days after inoculation, no evidence of brain disease was present, arguing against transmissibility.